Infection Defense May Spur Alzheimer’s

For years, a prevailing theory has been that one of the chief villains in Alzheimer’s disease has no real function other than as a waste product that the brain never properly disposed of.

The material, a protein called beta amyloid, or A-beta, piles up into tough plaques that destroy signals between nerves. When that happens, people lose their memory, their personality changes and they stop recognizing friends and family.

But now researchers at Harvard suggest that the protein has a real and unexpected function — it may be part of the brain’s normal defenses against invading bacteria and other microbes.

Other Alzheimer’s researchers say the findings, reported in the current issue of the journal PLoS One, are intriguing, though it is not clear whether they will lead to new ways of preventing or treating the disease.

The new hypothesis got its start late one Friday evening in the summer of 2007 in a laboratory at Harvard Medical School. The lead researcher, Rudolph E. Tanzi, a neurology professor who is also director of the genetics and aging unit at Massachusetts General Hospital, said he had been looking at a list of genes that seemed to be associated with Alzheimer’s disease.

To his surprise, many looked just like genes associated with the so-called innate immune system, a set of proteins the body uses to fight infections. The system is particularly important in the brain, because antibodies cannot get through the blood-brain barrier, the membrane that protects the brain. When the brain is infected, it relies on the innate immune system to protect it...

The article refers to the "innate" and "adaptive" immune system. The "innate" portion relies upon AMP and certain proteins to provide targeted protection against common microbial pathogens. The "innate" immune system is available in the brain. The "adaptive" part that reacts to antigenic exposure to produce antibody responses is largely excluded by the blood brain barrier. When the "innate" substances react with a microbial invader, the products remaining behind are the beta amyloid proteins. They are "normal" artifacts of the anti-microbial reaction. My interpretation is that a build up of amyloid plaques is an indication of a sustained attack on brain tissue by microbial pathogens that have successfully passed into the brain. Perhaps the way to ward off Alzheimer's would be to find a means of keeping the pathogens out.

From the article:

In summary, our finding that Aβ is an antimicrobial peptide is the first evidence that the species responsible for amyloidosis may have a normal function. This stands in stark contrast to current models, which assume β-amyloid deposition to be an accidental process resulting from the abnormal behavior of an incidental product of catabolism. Our data suggest increased Aβ generation, and resulting AD pathology, may be a mediated by a response of the innate immune system to a perceived infection. This model has important implications for current and future AD treatment strategies. First, it raises the possibility of preventing amyloidosis from initiating by pre-emptive targeting of pathogens/insults that stimulate the brain's innate immune system. Second, our model identifies the inflammatory pathways of the innate immune system as targets for modulating Aβ generation/accumulation. The target pathways implicated here are downstream of the inflammatory trigger. Thus, this approach would likely be useful independently of the involvement of infectious agents in AD pathology.

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